By
Kevin E. Noonan —

A day after Myriad
Genetics sued Ambry Genetics for patent infringement, the company filed
suit in the District of Utah, Central Divisions against Gene by Gene Ltd. (Case
No. 2:13-cv-00643-EJF; complaint).  The complaint is nearly identical
to Myriad's complaint against Ambry Genetics, and once again Myriad is joined
by the University of Utah Research Foundation, the Trustees of the University
of Pennsylvania, HSC Research and Development Limited Partnership, and
Endorecherche Inc.

This Complaint
alleges that:

Defendant, through its DNA Traits division, began offering its BRCA1 and BRCA2 analysis
as part of its testing menu on June 13, 2013.  Defendant offers stand-alone
tests comprising full gene sequencing and analyses for the BRCA 1 and BRCA 2
genes.

Defendant is infringing, contributing to the infringement of, and/or inducing
others to infringe
[each of the nine asserted patents] by making, manufacturing, promoting,
marketing, advertising, distributing, offering for sale and selling and/or
causing to be offered or sold BRCA1 and BRCA2 products that infringe at least
the following claim of
[each of the patents in suit] literally and/or under the doctrine of
equivalents [].

The specific claims
Myriad alleges are infringed include the following:  claim 6 of U.S. Patent No. 5,709,999; claims 6, 16 and 17 of  U.S. Patent No. 5,747,282; claims 7, 8,
12, 23, and 26 of U.S.
Patent No. 5,753,441; claims 29 and 30 of U.S. Patent No. 5,837,492; claim 4 of U.S. Patent No. 6,033,857; claims 2, 3 and 4 of U.S. Patent No. 5,654,155; claims 2, 3,
4, 5, 6, and 7 of U.S.
Patent No. 5,750,400; claim 5 of U.S. Patent No. 6,951,721; and claims 3, 4, 5, 6, 7, 8, 11, 14,
17, 18, 19 of U.S. Patent No. 7,250,497.  Missing from the complaint against Gene by Gene are allegations of
infringement of claims 32 and 33 of U.S. Patent No. 6,051,379
asserted in the complaint Myriad filed yesterday against Ambry Genetics.

Once again, Myriad
and its co-plaintiffs request judgment of patent infringement, an injunction,
an accounting and damages, delivery for destruction of all "products"
that infringe any of the asserted claims, a finding of willful infringement,
and a request for attorneys' fees, enhanced damages and costs of suit, as well
as a jury trial.

The genetic
diagnostics community awaits the identity of the next of its members who
announced plans to market BRCA gene testing that Myriad decides to sue.  It appears that Myriad is serious about
protecting its intellectual property until the company's patents expire over
the next few years.

By
Kevin E. Noonan —

Today
Myriad Genetics sued Ambry Genetics, Corp. in the District of Utah, Central Division
for patent infringement of ten patents relating to genetic diagnostic testing
(Case No. 2:13-cv-00640-RJS; complaint).  Ambry
Genetics was one of the first companies to announce that it would provide genetic diagnostic testing for the BRCA 1 and BRCA 2
genes on the day the U.S. Supreme Court announced its decision in AMP v. Myriad Genetics on the question
of "whether human genes are patentable."  Joining Myriad as plaintiffs are the
University of Utah Research Foundation, the Trustees of the University of
Pennsylvania, HSC Research and Development Limited Partnership, and
Endorecherche Inc.

The
Complaint alleges that:

Defendant began offering its
BRCA1 and BRCA2 analysis as part of its cancer testing menu on June 13, 2013.  On information and belief, Defendant offers stand-alone tests comprising full
gene sequencing and deletion/duplication analyses for the BRCA 1 and BRCA 2
genes.  On information and belief, Defendant also offers full gene sequencing
and deletion/duplication analyses for the BRCA 1 and BRCA 2 genes as part of
multiple hereditary cancer panels that test cancer susceptibility using
next-generation sequencing technology.

Defendant is infringing,
contributing to the infringement of, and/or inducing others to infringe the '999
patent by making, manufacturing, promoting, marketing, advertising, distributing,
offering for sale and selling and/or causing to be offered or sold certain
BRCA1, BRCA2, BRCAPlus, BreastNext, OvaNext, and CancerNext products that
infringe at least the following claim of [each of the patents in suit]
literally and/or under the doctrine of equivalents for ten patents owned or
licensed to Myriad.

The
specific claims Myriad alleges are infringed include the following:

First
Claim for Relief:  U.S. Patent No.
5,709,999

Claim 6: A method for detecting a
germline alteration in a BRCA1 gene, said alteration selected from the group
consisting of the alterations set forth in Tables 12A, 14, 18 or 19 in a human
which comprises analyzing a sequence of a BRCA1 gene or BRCA1 RNA from a human
sample or analyzing a sequence of BRCA1 cDNA made from mRNA from said human
sample with the proviso that said germline alteration is not a deletion of 4
nucleotides corresponding to base numbers 4184-4187 of SEQ ID NO:1, wherein a
germline alteration is detected by amplifying all or part of a BRCA1 gene in
said sample using a set of primers specific for a wild-type BRCA1 gene to
produce amplified BRCA1 nucleic acids and sequencing the amplified BRCA1
nucleic acids.

Second
Claim for Relief: U.S. Patent No. 5,747,282

Claim 6: An
isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino
acid sequence set forth in SEQ ID NO:2, 
wherein said DNA has the nucleotide sequence set forth in SEQ ID NO:1,
and having at least 15 nucleotides of the DNA of claim 2.

Claim 16: A pair
of single-stranded DNA primers for determination of a nucleotide sequence of a
BRCA1 gene by a polymerase chin reaction, the sequence of said primers being
derived from human chromosome 17q, wherein the use of said primers in a
polymerase chain reaction results in the synthesis of DNA having all or part of
the sequence of the BRCA1 gene.

Claim 17: The
pair of primers of claim 16 wherein said BRCA1 gene has the nucleotide sequence
set forth in SEQ ID NO:1.

Third Claim for Relief: U.S. Patent No. 5,753,441

Claim 7: A method
for screening germline of a human subject for an alteration of a BRCA1 gene
which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a
tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from
said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1
RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1
gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an
alteration in the BRCA1 gene in said subject, wherein a germline nucleic acid
sequence is compared by hybridizing a BRCA1 gene probe which specifically
hybridizes to a BRCA1 allele to genomic DNA isolated from said sample and
detecting the presence of a hybridization product wherein a presence of said
product indicates the presence of said allele in the subject.

Claim 8: A method
for screening germline of a human subject for an alteration of a BRCA1 gene
which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA from a
tissue sample from said subject or a sequence of BRCA1 cDNA made from mRNA from
said sample with germline sequences of wild-type BRCA1 gene, wild-type BRCA1
RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the BRCA1
gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an
alteration in the BRCA1 gene in said subject, wherein a germline nucleic acid
sequence is compared by amplifying all or part of a BRCA1 gene from said sample
using a set of primers to produce amplified nucleic acids and sequencing the
amplified nucleic acid.

Claim 12: A
method for screening germline of a human subject for an alteration of a BRCA1
gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA
from a tissue sample from said subject or a sequence of BRCA1 cDNA made from
mRNA from said sample with germline sequences of wild-type BRCA1 gene, wild-type
BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the sequence of the
BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from wild-type indicates an
alteration in the BRCA1 gene in said subject, wherein a germline nucleic acid
sequence is compared by amplifying BRCA1 nucleic acids from said sample to
produce amplified nucleic acids, hybridizing the amplified nucleic acids to a
BRCA1 DNA probe specific for a BRCA1 allele and detecting the presence of a
hybridization product, wherein the presence of said product indicates the
presence of said allele in the subject.

Claim 23. A
method for detecting a germline alteration in a BRCA1 gene, said alteration
selected from the group consisting of the alterations set forth in Tables 11
and 12 which comprises analyzing a sequence of the BRCA1 gene or BRCA1 RNA from
a human sample or analyzing the sequence of BRCA1 CDNA made from mRNA from said
sample, wherein a germline alteration is detected by amplifying all or part of
a BRCA1 gene in said sample using a set of primers to produce amplified nucleic
acids and sequencing the amplified nucleic acids.

Claim 26.  A method for detecting a germline alteration
in a BRCA1 gene, said alteration selected from the group consisting of the
alterations set forth in Tables 11 and 12 which comprises analyzing a sequence
of the BRCA1 gene or BRCA1 RNA from a human sample or analyzing the sequence of
BRCA1 CDNA made from mRNA from said sample, wherein a germline alteration is
detected by amplifying BRCA1 gene nucleic acids in said sample, hybridizing the
amplified nucleic acids to a BRCA1 DNA probe specific for one of said
alterations and detecting the presence of a hybridization product, wherein the
presence of said product indicates the presence of said alteration.

Fourth Claim for Relief: U.S. Patent No. 5,837,492

Claim 29. A pair
of single-stranded DNA primers of at least 15 nucleotides in length for
determination of the nucleotide sequence of a BRCA2 gene by a polymerase chain
reaction, the sequence of said primers being isolated from human chromosome 13,
wherein the use of said primers in a polymerase chain reaction results in the
synthesis of DNA comprising all or at least 15 contiguous nucleotides of the
BRCA2 gene.

Claim 30. The
pair of primers of claim 29 wherein said BRCA2 gene has the nucleotide sequence
set forth in SEQ ID NO:1.

Fifth Claim for Relief: U.S. Patent No. 6,033,857

Claim 4. A method
for diagnosing a predisposition for breast cancer in a human subject which
comprises comparing the germline sequence of the BRCA2 gene or the sequence of
its mRNA in a tissue sample from said subject with the germline sequence of the
wild-type BRCA2 gene or the sequence of its mRNA, wherein an alteration in the
germline sequence of the BRCA2 gene or the sequence of its mRNA of the subject
indicates a predisposition to said cancer, wherein the detection in the
alteration in the germline sequence is determined by an assay selected from the
group consisting of (a) observing shifts in electrophoretic mobility of single-stranded
DNA on non-denaturing polyacrylamide gels, (b) hybridizing a BRCA2 gene probe
to genomic DNA isolated from said tissue sample, (c) hybridizing an
allele-specific probe to genomic DNA of the tissue sample, (d) amplifying all
or part of the BRCA2 gene from said tissue sample to produce an amplified
sequence and sequencing the amplified sequence, (e) amplifying all or part of
the BRCA2 gene from said tissue sample using primers for a specific BRCA2
mutant allele, (f) molecularly cloning all or part of the BRCA2 gene from said
tissue sample to produce a cloned sequence and sequencing the cloned sequence,
(g) identifying a mismatch between (1) a BRCA2 gene or a BRCA2 mRNA isolated
from said tissue sample, and (2) a nucleic acid probe complementary to the
human wild-type BRCA2 gene sequence, when molecules (1) and (2) are hybridized
to each other to form a duplex, (h) amplification of BRCA2 gene sequences in
said tissue sample and hybridization of the amplified sequences to nucleic acid
probes which comprise wild-type BRCA2 gene sequences, (i) amplification of
BRCA2 gene sequences in said tissue sample and hybridization of the amplified
sequences to nucleic acid probes which comprise mutant BRCA2 gene sequences,
(j) screening for a deletion mutation in said tissue sample, (k) screening for
a point mutation in said tissue sample, (l) screening for an insertion mutation
in said tissue sample, (m) in situ hybridization of the BRCA2 gene of said
tissue sample with nucleic acid probes which comprise the BRCA2 gene.

Sixth Claim for Relief: U.S. Patent No. 5,654,155

Claim 2. A method
of identifying individuals having a BRCA1 gene with a BRCA1 coding sequence not
associated with breast or ovarian cancer comprising:
    a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
    b) sequencing said amplified fragment by dideoxy
sequencing;
    c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
    d) comparing the sequence of said amplified DNA to
the sequence of SEQ. ID. NO: 1;
    e) determining the presence or absence of each of
the following polymorphic variations in said individual's BRCA1 coding
sequence:
    AGC and ACT at position 2201, TTG and CTG at
position 2430,  CCG and CTG at position
2731,  GAA and GGA at position 3232, AAA
and AGA at position 3667, TCT and TCC at position 4427, and ACT and GGT at
position 4956;
    f) determining any sequence differences between
said individual's BRCA1 coding sequences and SEQ. ID. NO: 1 wherein the
presence of any of the said polymorphic variations and the absence of a
polymorphism outside of positions 2201, 2430, 2731, 3232, 3667, 4427, and 4956,
is correlated with an absence of increased genetic susceptibility to breast or
ovarian cancer resulting from a BRCA1 mutation in the BRCA1 coding sequence.

Claim 3. A method
according to claim 2 wherein said oligonucleotide primer is labeled with a
radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent
label or an enzyme label

Claim 4. A method
of detecting an increased genetic susceptibility to breast and ovarian cancer
in an individual resulting from the presence of a mutation in the BRCA1 coding
sequence, comprising:
    a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
    b) sequencing said amplified fragment by dideoxy
sequencing;
    c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
    d) comparing the sequence of said amplified DNA to
the sequence of SEQ. ID. NO: 1;
    e) determining any sequence differences between
said individual's BRCA1 coding sequences and SEQ. ID. NO: 1 to determine the
presence or absence of polymorphisms in said individual's BRCA coding sequences
wherein a polymorphism which is not any of the following:
    AGC or AGT at position 2201, TTG or CTG at position
2430, CCG or CTG at position 2731, GAA or GGA at position 3232, AAA or AGA at
position 3667, TCT or TCC at position 4427, and AGT or GGT at position 4956;
    is correlated with the potential of increased
genetic susceptibility to breast or ovarian cancer resulting from a BRCA1
mutation in the BRCA1 coding sequence.

Seventh Claim for Relief: U.S. Patent No. 5,750,400

Claim 2. A method
of identifying individuals having a BRCA1 gene with a BRCA1 coding sequence not
associated with ovarian or breast cancer disease, comprising:
    (a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
    (b) sequencing said amplified DNA fragment by
dideoxy sequencing;
    (c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
    (d) comparing the sequence of said amplified DNA
fragment to a BRCA1^(omi) DNA sequence selected from the group
consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
NO: 5;
    (e) determining the presence or absence of each of
the following polymorphic variations in said individual's BRCA1 coding
sequence:
        (i) C and T at position 2201,
        (ii) T and C at position 2430,
        (iii) C and T at position 2731,
        (iv) A and G at position 3232,
        (v) A and G at position 3667,
        (vi) T and C at position 4427, and
        (vii) A and G at position 4956;
    (f) determining any sequence differences between
said individual's BRCA1 coding sequences and a BRCA1^(omi) DNA
sequence selected from the group consisting of: SEQ ID NO: 1 together with SEQ
ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together with
SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID NO:
5, SEQ ID NO: 3 and SEQ ID NO: 5, wherein the presence of said polymorphic
variations and the absence of a variation outside of positions 2201, 2430,
2731, 3232, 3667, 4427 and 4956 is correlated with an absence of increased
genetic susceptibility to breast or ovarian cancer resulting from a BRCA1
mutation in the BRCA1 coding sequence.

Claim 3. A method
of identifying individuals having a BRCA1 gene with a BRCA1 coding sequence not
associated with ovarian or breast cancer disease, comprising:
    (a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
    (b) sequencing said amplified DNA fragment by
dideoxy sequencing;
    (c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
    (d) comparing the sequence of said amplified DNA
fragment to a BRCA1^(omi)) DNA sequence selected from the group
consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
NO: 5;
    (e) determining the presence or absence of each of
the following polymorphic variations in said individual's BRCA1 coding
sequence:
        (i) C and T at position 2201,
        (ii) T and C at position 2430,
        (iii) C an d T at position 2731,
        (iv) A and G at position 3232,
        (v) A and G at position 3667,
        (vi) T and C at position 4427, and
        (vii) A and G at position 4956; and
    (f) determining any sequence differences between
said individual's BRCA1 coding sequences and a BRCA1^(omi) DNA
sequence selected from the group consisting of: SEQ ID NO: 1 together with SEQ
ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together with
SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID NO:
5, SEQ ID NO: 3 and SEQ ID NO: 5, wherein the presence of said polymorphic
variations and the absence of a variation outside of positions 2201, 2430,
2731, 3232, 3667, 4427 and 4956 is correlated with an absence of increased
genetic susceptibility to breast or ovarian cancer resulting from a BRCA1
mutation in the BRCA1 coding sequence;
    wherein codon variations occur at the following
frequencies, respectively, in a Caucasian population of individuals with no
family history of breast or ovarian cancer:
        (i) at position 2201, C and T occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
        (ii) at position 2430, T and C occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
        (iii) at position 2731, C and T occur at
frequencies from about 25 to about 35%, and from about 65 to about 75%,
respectively;
        (iv) at position 3232, A and G occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
        (v) at position 3667, A and G occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
        (vi) at position 4427, T and C occur at frequencies
from about 45 to about 55%, and from about 45 to about 55%, respectively; and
        (vii) at position 4956, A and G occur at
frequencies from about 35 to about 45%, and from about 55 to about 65%,
respectively.

Claim 4. A method
according to claims 2 or 3, wherein said oligonucleotide primer is labeled with
a radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent
label, or an enzyme label.

Claim 5. A method
of detecting an increased genetic susceptibility to breast and ovarian cancer
in an individual resulting from the presence of a mutation in the BRCA1 coding
sequence, comprising:
    (a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
    (b) sequencing said amplified DNA fragment by
dideoxy sequencing;
    (c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
    (d) comparing the sequence of said amplified DNA
fragment to a BRCA1^(omi) DNA sequence selected from the group
consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
NO: 5;
    (e) determining any sequence differences between
said individual's BRCA1 coding sequences and a BRCA1^(omi) DNA
sequence selected from the group consisting of: SEQ. ID. NO.: 1 together with
SEQ ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together
with SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID
NO: 5, SEQ ID NO: 3 and SEQ ID NO: 5 in order to determine the presence or
absence of base changes in said individual's BRCA1 coding sequence wherein a
base change which is not any one of the following:
        (i) C and T at position 2201,
        (ii) T and C at position 2430,
        (iii) C and T at position 2731,
        (iv) A and G at position 3232,
        (v) A and G at position 3667,
        (vi) T and C at position 4427, and
        (vii) A and G at position 4956, is correlated with
the potential of increased genetic susceptibility to breast or ovarian cancer
resulting from a BRCA1 mutation in the BRCA1 coding sequence.

Claim 6. A method
of detecting an increased genetic susceptibility to breast and ovarian cancer
in an individual resulting from the presence of a mutation in the BRCA1 coding
sequence, comprising:
    (a) amplifying a DNA fragment of an individual's
BRCA1 coding sequence using an oligonucleotide primer which specifically
hybridizes to sequences within the gene;
    (b) sequencing said amplified DNA fragment by
dideoxy sequencing;
    (c) repeating steps (a) and (b) until said
individual's BRCA1 coding sequence is completely sequenced;
    (d) comparing the sequence of said amplified DNA
fragment to a BRCA1^(omi) DNA sequence selected from the group
consisting of: SEQ ID NO: 1 together with SEQ ID NO: 3, SEQ ID NO: 1 together
with SEQ ID NO: 5, SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 1
together with SEQ ID NO: 3 together with SEQ ID NO: 5, SEQ ID NO: 3 and SEQ ID
NO: 5;
    (e) determining any sequence differences between
said individual's BRCA1 coding sequences and a BRCA1^(omi) DNA
sequence selected from the group consisting of: SEQ ID NO: 1 together with SEQ
ID NO: 3, SEQ ID NO: 1 together with SEQ ID NO: 5, SEQ ID NO: 3 together with
SEQ ID NO: 5, SEQ ID NO: 1 together with SEQ ID NO: 3 together with SEQ ID NO:
5, SEQ ID NO: 3 and SEQ ID NO: 5 in order to determine the presence or absence
of base changes in said individual's BRCA1 coding sequence wherein a base
change which is not any one of the following:
        (i) C and T at position 2201,
        (ii) T and C at position 2430,
        (iii) C and T at position 2731,
        (iv) A and G at position 3232,
        (v) A and G at position 3667,
        (vi) T and C at position 4427, and
        (vii) A and G at position 4956, is correlated with
the potential of increased genetic susceptibility to breast or ovarian cancer
resulting from a BRCA1 mutation in the BRCA1 coding sequence, wherein codon
variations occur at the following frequencies, respectively, in a Caucasian
population of individuals with no family history of breast or ovarian cancer:
        (i) at position 2201, C and T occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
        (ii) at position 2430, T and C occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
        (iii) at position 2731, C and T occur at
frequencies from about 25 to about 35%, and from about 65 to about 75%,
respectively;
        (iv) at position 3232, A and G occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
        (v) at position 3667, A and G occur at frequencies
from about 35 to about 45%, and from about 55 to about 65%, respectively;
        (vi) at position 4427, T and C occur at frequencies
from about 45 to about 55%, and from about 45 to about 55%, respectively; and
        (vii) at position 4956, A and G occur at
frequencies from about 35 to about 45%, and from about 55 to about 65%,
respectively.

Claim 7. A method
according to claims 5 or 6, wherein said oligonucleotide primer is labeled with
a radiolabel, a fluorescent label, a bioluminescent label, a chemiluminescent
label, or an enzyme label.

Eighth Claim for Relief: U.S. Patent No. 6,051,379

Claim 32. A
method of detecting a predisposition or higher susceptibility to cancer in an
individual, comprising:
    (a) digesting DNA from an individual to obtain DNA
fragments;
    (b) separating said DNA fragments;
    (c) detecting a DNA fragment containing nucleotide
number 2192, 3772, 5193, 5374, 6495 or 6909 of the BRCA2 gene sequence or a
sequence variation at nucleotide number 2192, 3772, 5193, 5374, 6495 or 6909 of
the BRCA2 gene sequence by sequencing;
    (d) comparing the sequence of said fragment with
the BRCA2 gene sequence to determine the presence or absence of a sequence
variation at nucleotide number 2192, 3772, 5193, 5374, 6495 or 6909, wherein
the presence of a sequence variation indicates a predisposition or higher
susceptibility to cancer.

Claim 33. A
method according to claim 32 further comprising amplifying said DNA fragments
prior to the detecting step (c).

Ninth Claim for Relief: U.S. Patent No. 6,951,721

Claim 5. A method
for determining an omi haplotype of a human BRCA1 gene comprising: (a)
determining the nucleotide sequence of the BRCA1 gene or fragment thereof from
at least one female individual with a family history which indicates a
predisposition to breast cancer, (b) comparing the determined nucleotide
sequence from said female individual to SEQ ID NO: 263, and (c) determining the
presence of the following nucleotide variations: thymine at nucleotides 2201
and 2731, cytosine at nucleotides 2430 and 4427, and guanine at nucleotides
3232, 3667 and 4956, wherein the presence of the nucleotide variations in the
determined nucleotide sequence indicates the omi1 haplotype,  further comprising comparing the determined
nucleotide sequence to SEQ ID NO: 265.

Tenth Claim for Relief: U.S. Patent No. 7,250,497

Claims 3, 4, 5, 6, 7, 8, 11, 14, 17, 18, 19

[Claim 1. An isolated
nucleic acid comprising SEQ ID NO:6, and the complement thereof.

Claim 2. The isolated nucleic acid of claim 1, wherein
said isolated nucleic acid comprises SEQ ID NO:37, or the complement thereof.]

Claim 3. A method of making the isolated nucleic
acid of claim 2 comprising amplifying genomic DNA isolated from a sample
obtained from a human patient.

Claim 4. A method of making the isolated nucleic
acid of claim 1 comprising amplifying genomic DNA isolated from a sample
obtained from a human patient.

Claim 5. The method of claim 4, wherein said sample
is a blood sample.

Claim 6. The method of claim 4, wherein said
amplification is by the polymerase chain reaction.

Claim 7. The method of claim 4, wherein said
patient is being evaluated for an enhanced risk of cancer.

Claim 8. The method of claim 4, wherein said cancer
is breast or ovarian cancer.

Claim 11. A method of making the isolated nucleic
acid of claim 9 comprising amplifying genomic DNA isolated from a sample
obtained from a human patient.

Claim 14. A method of making the isolated nucleic
acid of claim 12 comprising amplifying genomic DNA isolated from a sample
obtained from a human patient.

Claim 17. A method of making the isolated nucleic
acid of claim 15 comprising amplifying genomic DNA isolated from a sample
obtained from a human patient.

Claim 18. The isolated nucleic acid of claim 1,
wherein said isolated nucleic acid comprises SEQ ID NO:41, or the complement
thereof.

Claim 19. A
method of making the isolated nucleic acid of claim 18 comprising amplifying
genomic DNA isolated from a sample obtained from a human patient.

These method claims differ from the claims
invalidated by the District Court in the Myriad
case and affirmed by the Federal Circuit, which recited as limitations merely "comparing"
an individual's BRCA gene sequence with the "normal" one, and thus
Myriad is less likely to be estopped from asserting these claims against Ambry.

Myriad's Relief Requested in its complaint includes
judgment of patent infringement, an injunction, an accounting and damages, delivery for destruction of all "products"
that infringe any of the asserted claims, a finding of willful infringement,
and a request for attorneys' fees, enhanced damages and costs of suit.  Myriad also demands a jury trial.

As has been discussed in earlier posts, some of
these claims (e.g., directed to oligonucleotides)
may be subject to invalidation on novelty grounds (see "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims").  In addition, not
all assignees are named in the complaint (most notably the U.S. Government "as
represented by the Secretary of Health") and insofar as any of them are
adjudged to be indispensible parties, any unwillingness to be joined might cause
Myriad procedural difficulties.  But it
is significant that Myriad has decided to assert these patents, and its
continued ability to do so illustrates one of the generally unappreciated
aspects of the Myriad case.  Plaintiffs in that case and their supporters,
the ACLU and Public Patent Foundation, chose the claims against which to
assert their challenge to the validity of Myriad's patents.  Which means, of course, that they chose not to challenge the claims Myriad is
now asserting, leaving the plaintiffs (including breast cancer patients)
without the full and complete remedy they no doubt were promised and that the
press seems to believe the Supreme Court's June 13 decision gave
them (see "Reaction to Supreme Court's Decision in AMP v. Myriad" and "Does the Myriad Decision Presage a Golden Age of Patent-Free Personalized Medicine?").  Instead, plaintiffs challenged claims to isolated DNA (characterized as "genes"),
even though such claims are not infringed by the practice of modern genetic
diagnostic methods.  The result of these strategic (and ultimately
political or at least public-relations focused) decisions is that Myriad owns
or has licensed patents that presumptively preclude Ambry Genetics or any other
provider from offering BRCA gene-directed genetic diagnostic tests until these
patents expire in the next few years.  In
short, the parties are in exactly the same position that existed prior to the
Myriad suit.  While this outcome should
have been expected, it raises doubts about the consensus narrative of what "everybody
knows" this case was all about.